tbuckley/cabot-search huggingface dataset:
Orbitofrontal cortex-hippocampus potentiation mediates relief for depression: A randomized double-blind trial and TMS-EEG study
Authors: Sizhu Han, Xing-Xing Li, Shuochi Wei, Di Zhao, Jinjun Ding, Yongming Xu, Chang Yu, Zan Chen, Dong-Sheng Zhou, Ti-Fei Yuan
Journal: Cell Reports Medicine (2023)

It has been 15 years since repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) was approved by the FDA for clinical depression treatment. Yet, the underlying mechanisms for rTMS-induced depression relief are not fully elucidated. This study analyzes TMS-electroencephalogram (EEG) data from 64 healthy control (HC) subjects and 53 patients with major depressive disorder (MDD) before and after rTMS treatment. Prior to treatment, patients with MDD have lower activity in the DLPFC, the hippocampus (HPC), the orbitofrontal cortex (OFC), and DLPFC-OFC connectivity compared with HCs. Following active rTMS treatment, patients with MDD show a significant increase in the DLPFC, HPC, and OFC. Notably, the increase in HPC activity is specifically associated with amelioration of depressive symptoms but not anxiety or sleep quality. The orbitofrontal-hippocampal pathway plays a crucial role in mediating depression relief following rTMS treatment. These findings suggest potential alternative targets for brain stimulation therapy against depression (chictr.org.cn: ChiCTR2100052007).
Rigorous and rapid evidence assessment in digital health with the evidence DEFINED framework
Authors: Jordan Silberman, Paul Wicks, Smit Patel, Siavash Sarlati, Siyeon Park, Igor O. Korolev, Jenna R. Carl, Jocelynn T. Owusu, Vimal Mishra, Manpreet Kaur, Vincent J. Willey, Madalina L. Sucala, Tim R. Campellone, Cindy Geoghegan, Isaac R. Rodriguez-Chavez, Benjamin Vandendriessche, Siyeon Park, Vimal Mishra, Isaac R. Rodriguez-Chavez, Jennifer C. Goldsack
Journal: npj Digital Medicine (2023)

Abstract Dozens of frameworks have been proposed to assess evidence for digital health interventions (DHIs), but existing frameworks may not facilitate DHI evidence reviews that meet the needs of stakeholder organizations including payers, health systems, trade organizations, and others. These organizations may benefit from a DHI assessment framework that is both rigorous and rapid. Here we propose a framework to assess Evidence in D igital health for EF fectiveness of IN terventions with E valuative D epth (Evidence DEFINED). Designed for real-world use, the Evidence DEFINED Quick Start Guide may help streamline DHI assessment. A checklist is provided summarizing high-priority evidence considerations in digital health. Evidence-to-recommendation guidelines are proposed, specifying degrees of adoption that may be appropriate for a range of evidence quality levels. Evidence DEFINED differs from prior frameworks in its inclusion of unique elements designed for rigor and speed. Rigor is increased by addressing three gaps in prior frameworks. First, prior frameworks are not adapted adequately to address evidence considerations that are unique to digital health. Second, prior frameworks do not specify evidence quality criteria requiring increased vigilance for DHIs in the current regulatory context. Third, extant frameworks rarely leverage established, robust methodologies that were developed for non-digital interventions. Speed is achieved in the Evidence DEFINED Framework through screening optimization and deprioritization of steps that may have limited value. The primary goals of Evidence DEFINED are to a) facilitate standardized, rapid, rigorous DHI evidence assessment in organizations and b) guide digital health solutions providers who wish to generate evidence that drives DHI adoption.
Artificial intelligence-driven drug development against autoimmune diseases
Authors: Philippe Moingeon
Journal: Trends in Pharmacological Sciences (2023)

Artificial intelligence (AI)-based predictive models are being used to foster a precision medicine approach to treat complex chronic diseases such as autoimmune and autoinflammatory disorders (AIIDs). In the past few years the first models of systemic lupus erythematosus (SLE), primary Sjögren syndrome (pSS), and rheumatoid arthritis (RA) have been produced by molecular profiling of patients using omic technologies and integrating the data with AI. These advances have confirmed a complex pathophysiology involving multiple proinflammatory pathways and also provide evidence for shared molecular dysregulation across different AIIDs. I discuss how models are used to stratify patients, assess causality in pathophysiology, design drug candidates in silico, and predict drug efficacy in virtual patients. By relating individual patient characteristics to the predicted properties of millions of drug candidates, these models can improve the management of AIIDs through more personalized treatments.
Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model
Authors: Diana Rose E Ranoa, Preeti Sharma, Claire P Schane, Amber N Lewis, Edward Valdez, Venkata V V R Marada, Marlies V Hager, Will Montgomery, Steven P Wolf, Karin Schreiber, Hans Schreiber, Keith Bailey, Timothy M Fan, Paul J Hergenrother, Edward J Roy, David M Kranz
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. In contrast, CAR-T cell efficacy against solid tumors has been difficult to achieve. Methods To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc . The efficacy of four Tn-dependent CARs with varying affinity to Tn antigen, and each containing CD28/CD3ζ cytoplasmic domains, were compared in vitro and in vivo in this study. Results In line with many observations about the impact of aberrant O-linked glycosylation, the ID8 Cosmc knock-out (ID8 Cosmc -KO) exhibited more rapid tumor progression compared with wild-type ID8. Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8 Cosmc -KO tumors. Tumor regression could be achieved with a single intravenous dose of the CARs, but intraperitoneal administration was even more effective. The CAR-T cells persisted over a period of months, allowing CAR-treated mice to delay tumor growth in a re-challenge setting. The most effective CARs exhibited the highest affinity for antigen. Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10. Conclusion The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. Importantly, the most potent Tn-dependent CAR-T cells showed no evidence of toxicity in tumor-bearing mice in a syngeneic, immunocompetent system.
Understanding the scalability of personalised monitoring within indoor spaces
Authors: Graham Coulby, Alan Godfrey
Journal: npj Digital Medicine (2023)

Health and wellness/well-being are multifaceted topics further complicated when trying to understand the environmental impact. Typically, there has been a one size fits all approach when trying to understand the 3-way interaction, but that is a limited approach. Equally, measurement (of each) has often used a limited set of outcomes during short periods to provide insight. A more robust understanding of health and well-being within environments may require longitudinal/continuous assessment that holistically targets individuals. Therefore, there is a growing requirement for careful data management, individual-first methodologies, scalable research designs and new analytical approaches, e.g., artificial intelligence. That presents many challenges but interesting research opportunities for the field of digital medicine.
Disruption of axonal transport in neurodegeneration
Authors: Sarah H. Berth, Thomas E. Lloyd
Journal: Journal of Clinical Investigation (2023)

Neurons are markedly compartmentalized, which makes them reliant on axonal transport to maintain their health. Axonal transport is important for anterograde delivery of newly synthesized macromolecules and organelles from the cell body to the synapse and for the retrograde delivery of signaling endosomes and autophagosomes for degradation. Dysregulation of axonal transport occurs early in neurodegenerative diseases and plays a key role in axonal degeneration. Here, we provide an overview of mechanisms for regulation of axonal transport; discuss how these mechanisms are disrupted in neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, hereditary spastic paraplegia, amyotrophic lateral sclerosis, and Charcot-Marie-Tooth disease; and discuss therapeutic approaches targeting axonal transport.
OpenPBTA: The Open Pediatric Brain Tumor Atlas
Authors: Joshua A. Shapiro, Krutika S. Gaonkar, Stephanie J. Spielman, Candace L. Savonen, Chante J. Bethell, Run Jin, Komal S. Rathi, Yuankun Zhu, Laura E. Egolf, Bailey K. Farrow, Daniel P. Miller, Yang Yang, Tejaswi Koganti, Nighat Noureen, Mateusz P. Koptyra, Nhat Duong, Mariarita Santi, Jung Kim, Shannon Robins, Phillip B. Storm, Stephen C. Mack, Jena V. Lilly, Hongbo M. Xie, Payal Jain, Pichai Raman, Brian R. Rood, Rishi R. Lulla, Javad Nazarian, Adam A. Kraya, Zalman Vaksman, Allison P. Heath, Cassie Kline, Laura Scolaro, Angela N. Viaene, Xiaoyan Huang, Gregory P. Way, Steven M. Foltz, Bo Zhang, Anna R. Poetsch, Sabine Mueller, Brian M. Ennis, Michael Prados, Sharon J. Diskin, Siyuan Zheng, Yiran Guo, Shrivats Kannan, Angela J. Waanders, Ashley S. Margol, Meen Chul Kim, Derek Hanson, Nicholas Van Kuren, Jessica Wong, Rebecca S. Kaufman, Noel Coleman, Christopher Blackden, Kristina A. Cole, Jennifer L. Mason, Peter J. Madsen, Carl J. Koschmann, Douglas R. Stewart, Eric Wafula, Miguel A. Brown, Adam C. Resnick, Casey S. Greene, Jo Lynne Rokita, Jaclyn N. Taroni
Journal: Cell Genomics (2023)

Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, the Children's Brain Tumor Network (CBTN) and Pacific Pediatric Neuro-Oncology Consortium (PNOC) created a systematic process for tumor biobanking, model generation, and sequencing with immediate access to harmonized data. We leverage these data to establish OpenPBTA, an open collaborative project with over 40 scalable analysis modules that genomically characterize 1,074 pediatric brain tumors. Transcriptomic classification reveals universal
Exercise, exerkines, and cardiometabolic health: from individual players to a team sport
Authors: Jeremy M. Robbins, Robert E. Gerszten
Journal: Journal of Clinical Investigation (2023)

Exercise confers numerous salutary effects that extend beyond individual organ systems to provide systemic health benefits. Here, we discuss the role of exercise in cardiovascular health. We summarize major findings from human exercise studies in cardiometabolic disease. We next describe our current understanding of cardiac-specific substrate metabolism that occurs with acute exercise and in response to exercise training. We subsequently focus on exercise-stimulated circulating biochemicals ("exerkines") as a paradigm for understanding the global health circuitry of exercise, and discuss important concepts in this emerging field before highlighting exerkines relevant in cardiovascular health and disease. Finally, this Review identifies gaps that remain in the field of exercise science and opportunities that exist to translate biologic insights into human health improvement.
Control of Blood Glucose and Diabetic Vascular Disease
Authors: Marvin D. Siperstein, Daniel W. Foster, Harvey C. Knowles, Rachmiel Levine, Leonard L. Madison, Jesse Roth
Journal: New England Journal of Medicine (1977)

Both the method of treating insulin-dependent diabetes and the relation between treatment and vascular complications have become subjects of renewed interest. There has been a long standing impression among many diabetologists that good control of blood glucose may prevent or delay the vascular complications of diabetes, When subjected to critical analysis, however, the various clinical studies attempting to demonstrate a beneficial effect of rigid glucose control have been, at best, inconclusive.1 , 2 Several recent publications have strongly implied that new findings in animals and man support the view that tight glucose regulation has a beneficial effect on diabetic vascular disease. The . . .
A Cloud Adult: The Staphylococcus aureus-Virus Interaction Revisited
Authors: Robert J. Sherertz
Journal: Annals of Internal Medicine (1996)

Background: Nasal carriage of Staphylococcus aureus is common among health care workers, but outbreaks caused by such carriers are relatively uncommon. We previously reported outbreaks of S. aureus skin infections that affected newborn infants and were attributed to an S. aureus nasal carrier who had had an associated upper respiratory tract infection (URI) during the outbreak period. Objective: To investigate the contribution of a nasal methicillin-resistant S. aureus (MRSA) carrier (physician 4) who contracted a URI to an outbreak of MRSA infections that involved 8 of 43 patients in a surgical intensive care unit during a 3-week period. Design: An epidemiologic study of an outbreak of MRSA infections and a quantitative investigation of airborne dispersal of S. aureus associated with an experimentally induced rhinoviral infection. Setting: A university hospital. Participants: 43 patients in a surgical intensive care unit and 1 physician. Measurements: Molecular typing was done, and risk factors for MRSA colonization were analyzed. Agar settle plates and volumetric air cultures were used to evaluate the airborne dispersal of S. aureus by physician 4 before and after a rhinoviral infection and with or without a surgical mask. Results: A search for nasal carriers of MRSA identified a single physician (physician 4); molecular typing showed that the MRSA strain from physician 4 and those from the patients were identical. Multivariate logistic regression analysis identified exposure to physician 4 and duration of ventilation as independent risk factors for colonization with MRSA (P < equals 0.008). Air cultures showed that physician 4 dispersed little S. aureus in the absence of a URI. After experimental induction of a rhinovirus URI, physician 4's airborne dispersal of S. aureus without a surgical mask increased 40-fold; dispersal was significantly reduced when physician 4 wore a mask (P < equals 0.015). Conclusions: Physician 4 became a "cloud adult," analogous to the "cloud babies" described by Eichenwald and coworkers who shed S. aureus into the air in association with viral URIs. Airborne dispersal of S. aureus in association with a URI may be an important mechanism of transmission of S. aureus.
Disparities in parental distress in a multicenter clinical trial for pediatric acute lymphoblastic leukemia
Authors: Puja J Umaretiya, Victoria B Koch, Yael Flamand, Rahela Aziz-Bose, Lenka Ilcisin, Ariana Valenzuela, Peter D Cole, Lisa M Gennarini, Justine M Kahn, Kara M Kelly, Thai Hoa Tran, Bruno Michon, Jennifer J G Welch, Joanne Wolfe, Lewis B Silverman, Kira Bona
Journal: JNCI Journal of the National Cancer Institute (2023)

Parent psychological distress during childhood cancer treatment has short- and long-term implications for parent, child, and family well-being. Identifying targetable predictors of parental distress is essential to inform interventions. We investigated the association between household material hardship (HMH), a modifiable poverty-exposure defined as housing, food, or utility insecurity, and severe psychological distress among parents of children aged 1-17 years with acute lymphoblastic leukemia (ALL) enrolled on the multicenter Dana-Farber ALL Consortium Trial 16-001.
Towards One Health surveillance of antibiotic resistance: characterisation and mapping of existing programmes in humans, animals, food and the environment in France, 2021
Authors: Lucie Collineau, Clémence Bourély, Léo Rousset, Anne Berger-Carbonne, Marie-Cécile Ploy, Céline Pulcini, Mélanie Colomb-Cotinat
Journal: Eurosurveillance (2023)

Background International organisations are calling for One Health approaches to tackle antimicrobial resistance. In France, getting an overview of the current surveillance system and its level of integration is difficult due to the diversity of surveillance programmes. Aim This study aimed to map and describe all French surveillance programmes for antibiotic resistance (ABR), antibiotic use (ABU) and antibiotic residues, in humans, animals, food and the environment, in 2021. Another objective was to identify integration points, gaps and overlaps in the system. Methods We reviewed the literature for surveillance programmes and their descriptions. To further characterise programmes found, semi-directed interviews were conducted with their coordinators. Results In total 48 programmes in the human (n = 35), animal (n = 12), food (n = 3) and/or the environment (n = 1) sectors were identified; 35 programmes focused on ABR, 14 on ABU and two on antibiotic residues. Two programmes were cross-sectoral. Among the 35 ABR programmes, 23 collected bacterial isolates. Bacteria most targeted were Escherichia coli (n = 17 programmes), Klebsiella pneumoniae (n = 13), and Staphylococcus aureus (n = 12). Extended-spectrum beta-lactamase-producing E. coli was monitored by most ABR programmes (15 of 35) in humans, animals and food, and is a good candidate for integrated analyses. ABU indicators were highly variable. Areas poorly covered were the environmental sector, overseas territories, antibiotic-resistant-bacterial colonisation in humans and ABU in companion animals. Conclusion The French surveillance system appears extensive but has gaps and is highly fragmented. We believe our mapping will interest policymakers and surveillance stakeholders. Our methodology may inspire other countries considering One Health surveillance of ABR.
Evidence Base for Health Care Strategies to Protect Vulnerable Patients During the COVID-19 Pandemic
Authors: Alyson Haslam, Vinay Prasad
Journal: JAMA Oncology (2023)

To the Editor The Editorial by Hoerger and colleagues 1 published recently in JAMA Oncology outlined 10 health care strategies to support patients who are vulnerable during the COVID-19 pandemic.We agree that strategies for protection are needed, but these strategies should be evidence based, which the 10 recommendations are not.Hoerger and colleagues 1 build on 3 previously suggested strategies: ventilation, filtration, and 2-way masking.Currently, to our knowledge, there are no randomized data on filtration systems in reducing COVID-19 transmission, although there are several randomized studies under way. 2,3Randomized data on the efficacy of masks are limited to 2 studies 4,5 that either reported no benefit or were biased, making it difficult to determine whether the small benefit reported was real or confounded.Neither study tested N95 masks.Moreover, whether masks work for months or years on end has not been assessed.Other interventions-antibody testing, prophylactics, education, or treatments for post-COVID-19 conditionhave yet to be tested to determine whether they have benefit.The authors 1 may contend that there are no downsides to these strategies.Yet there are downsides.Patients with cancer spend a good deal of time and financial resources on medical treatment.Engaging in these suggested strategies would further add to their time burden for medical treatment-time that could be spent enriching their quality of life with family or other meaningful and enjoyable activities.This additional time burden could be justified, however, if an evidence-based approach supported that these strategies lead to better patient outcomes.Because no randomized studies have been conducted, the time may be spent in vain.The financial aspect is an additional downside.There have been substantial financial contributions to implement these strategies, 1 which means that financial resources, which are limited, are being used to implement non-evidence-based strategies, when that money could have been used to conduct trials to generate evidence.We should not be complacent to accept recommendations based on intuition or basic laboratory or observational data, or because they are "imaginative," as it has been 3 years since the COVID-19 pandemic began.Rather, we should expect that recommendations are based on high-quality randomized clinical trial data with demonstrable efficacy.
Race, Lung Function, and the Historical Context of Prediction Equations
Authors: Lundy Braun, Ricky Grisson
Journal: JAMA Network Open (2023)

Alexander T. Moffett, MD; Cole Bowerman, MS; Sanja Stanojevic, PhD; Nwamaka D. Eneanya, MD; Scott D. Halpern, MD, PhD; Gary E. Weissman, MD
The Potential of Adaptive Radiotherapy for Patients With Head and Neck Cancer—Too Much or Not Enough?
Authors: Beth M. Beadle, Annie W. Chan
Journal: JAMA Oncology (2023)

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